macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss

Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss is an inherited disorder primarily affecting platelet formation and function, and in some cases, other organs such as the kidneys and ears. Caused by changes in the MYH9 gene, the condition is classified as a giant platelet disorder with a complex clinical presentation. It is inherited in an autosomal dominant manner, meaning a single altered copy of the gene can be sufficient to cause the condition. Although it is a rare disorder, affecting approximately 1 to 9 per million people, many individuals benefit from ongoing advancements in supportive care.

The clinical features of this condition center on abnormalities in platelet size and function. Most affected individuals have macrothrombocytopenia, giant platelets, and characteristic inclusion bodies in both leukocytes and neutrophils, leading to impaired platelet aggregation. In addition, some individuals may experience sensorineural hearing impairment, and there can be manifestations affecting the kidneys, such as progressive nephropathy, as well as potential cataracts and elevated liver enzymes. Not all individuals experience every feature, and severity varies considerably.

This disorder is caused by alterations in the MYH9 gene, which encodes a protein crucial for the normal function of non-muscle myosin. Changes in this protein affect the structure and function of megakaryocytes, leading to the production of abnormally large platelets with inclusion bodies. The condition is inherited in an autosomal dominant pattern, meaning that a single affected copy of MYH9 can result in the disorder, and an affected individual has a 50% chance of passing the mutation on to their children. That even within affected families, the spectrum and severity of symptoms can differ from one individual to another.

Currently, management focuses on supportive care and symptom management rather than curative interventions. Treatment is tailored to address the specific clinical features that a patient experiences, such as monitoring kidney function or managing bleeding episodes, and typically involves a multidisciplinary team. Alongside regular surveillance to identify complications early, genetic counseling is recommended for affected families to discuss inheritance and planning options. Patients should discuss treatment options with their healthcare team to determine the most appropriate care plan for their individual situation.

The long-term outlook for individuals with this condition varies widely, with outcomes influenced by the severity of kidney involvement, hearing impairment, and other systemic features. With current standards of care, many individuals live well into adulthood, and regular monitoring helps manage complications as they arise. Outcomes described in medical literature continue to evolve as standards of care improve, and the variability in clinical presentation means that not all individuals will experience the same progression of symptoms. Families often find it helpful to connect with genetic counselors and specialists familiar with the condition for ongoing guidance and support.

This is an active area of research, with numerous ongoing clinical trials exploring new treatment approaches that may enhance symptom management in the future. Individuals interested in clinical trials can search ClinicalTrials.gov or discuss eligibility with their care team.